Low‐grade inflammation in persons with recently diagnosed type 2 diabetes: The role of abdominal adiposity and putative mediators

Author:

Domazet Sidsel L.123ORCID,Olesen Thomas B.1,Stidsen Jacob V.1,Svensson Camilla K.34,Nielsen Jens S.12,Thomsen Reimar W.3,Jessen Niels5,Vestergaard Peter6,Andersen Mette K.7,Hansen Torben7,Brøns Charlotte8,Jensen Verena H.8ORCID,Vaag Allan A.89,Olsen Michael H.4,Højlund Kurt12ORCID

Affiliation:

1. Steno Diabetes Center Odense Odense University Hospital Odense Denmark

2. Department of Clinical Research University of Southern Denmark Odense Denmark

3. Department of Clinical Epidemiology Aarhus University and Aarhus University Hospital Aarhus Denmark

4. Department of Internal Medicine and Steno Diabetes Center Zealand Holbæk Hospital Holbæk Denmark

5. Steno Diabetes Center Aarhus Aarhus University Hospital Aarhus Denmark

6. Steno Diabetes Center North Denmark Aalborg University Hospital Aalborg Denmark

7. Novo Nordisk Foundation Centre for Basic Metabolic Research University of Copenhagen Copenhagen Denmark

8. Steno Diabetes Center Copenhagen Herlev Hospital Herlev Denmark

9. Lund University Diabetes Centre Malmö Sweden

Abstract

AbstractAimsTo determine the magnitude of the association between abdominal adiposity and low‐grade inflammation in persons with recently diagnosed type 2 diabetes (T2D) and to determine to what extent this association is mediated by low physical activity level, hyperinsulinaemia, hyperglycaemia, dyslipidaemia, hypertension, and comorbidities.Materials and MethodsWe measured waist circumference, clinical characteristics, and inflammatory markers i.e. tumour necrosis factor‐alpha (TNF‐α), interleukin‐6 (IL‐6), and high‐sensitivity C‐reactive protein (hsCRP), in >9000 persons with recently diagnosed T2D. We applied multiple mediation analysis using structural equation modelling, with adjustment for age and sex.ResultsWaist circumference as a proxy for abdominal adiposity was positively associated with all inflammatory markers. Hence, a one‐standard deviation (SD) increase in waist circumference (SD = 15 cm) was associated with a 22%, 35%, and 46% SD increase in TNF‐α (SD = 1.5 pg/mL), IL‐6 (SD = 4.4 pg/mL), and hsCRP (SD = 6.9 mg/L), respectively. The level of hyperinsulinaemia assessed by fasting C‐peptide was quantitatively the most important mediator, accounting for 9%–25% of the association between abdominal adiposity and low‐grade inflammation, followed by low physical activity (5%–7%) and high triglyceride levels (2%–6%). Although mediation of adiposity‐induced inflammation by greater comorbidity and higher glycated haemoglobin levels reached statistical significance, their impact was minor (1%–2%).ConclusionsIn persons with recently diagnosed T2D, there was a clear association between abdominal adiposity and low‐grade inflammation. A considerable part (20%–40%) of this association was mediated by other factors, with hyperinsulinaemia as a potentially important driver of adiposity‐induced inflammation in T2D.

Funder

Danish Agency for Science and Higher Education

Sundhedsstyrelsen

Diabetesforeningen

Region Syddanmark

Novo Nordisk Fonden

Publisher

Wiley

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